Yeast Endosulfines Control Entry into Quiescence and Chronological Life Span by Inhibiting Protein Phosphatase 2A

Séverine Bontron (1) , Malika Jaquenoud (1) , Stefania Vaga (2) , Nicolas Talarek (3) , Bernd Bodenmiller (2) , Ruedi Aebersold (2) , Claudio de Virgilio (1)

1 UNIFR - Université de Fribourg = University of Fribourg
2 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
3 IBGC - Institut de biochimie et génétique cellulaires

The TORC1 and PKA protein kinases are central elements of signaling networks that regulate eukary-otic cell proliferation in response to growth factors and/or nutrients. In yeast, attenuation of signaling by these kinases following nitrogen and/or carbon limitation activates the protein kinase Rim15, which orchestrates the initiation of a reversible cellular quiescence program to ensure normal chronological life span. The molecular elements linking Rim15 to distal readouts including the expression of Msn2/4-and Gis1-dependent genes involve the endosulfines Igo1/2. Here, we show that Rim15, analogous to the greatwall kinase in Xenopus, phosphorylates endo-sulfines to directly inhibit the Cdc55-protein phos-phatase 2A (PP2A Cdc55). Inhibition of PP2A Cdc55 preserves Gis1 in a phosphorylated state and consequently promotes its recruitment to and activation of transcription from promoters of specific nutrient-regulated genes. These results close a gap in our perception of and delineate a role for PP2A Cdc55 in TORC1-/PKA-mediated regulation of quiescence and chronological life span.

Domains: Molecular biology; Subcellular Processes [q-bio.SC]

Séverine Bontron, Malika Jaquenoud, Stefania Vaga, Nicolas Talarek, Bernd Bodenmiller, et al.. Yeast Endosulfines Control Entry into Quiescence and Chronological Life Span by Inhibiting Protein Phosphatase 2A. Cell Reports, 2013, 3 (1), pp.16-22. ⟨10.1016/j.celrep.2012.11.025⟩. ⟨hal-02134955⟩